The principal aim of this ongoing project is to determine the mode of action on the mammalian (rat) nervous system of drugs known to produce psychotogenic or hallucinogenic effects in humans. Two main groups of psychotogenic drugs are under study: the "psychedelics" (e.g., LSD and psilocin) and the "amphetamines". An associated goal is to study the basic neurobiology of neuronal systems (e.g., serotonergic, noradrenergic, dopaminergic) upon which the psychotogenic drugs act. The principal methods employed are that of single-cell recording, microiontophoresis, and electrical stimulation of anatomically identified pathways. Work during the current year has included: (1) Studies on adrenergic inputs to the dorsal raphe and their role in the control of serotonergic neuronal activity. (2) Further studies on serotonin autoreceptors as a site of action of hallucinogenic drugs. (3) Studies on the alteration of serotonin receptor sensitivity by chronic treatment with tricyclic antidepressants. (4) Studies on the physiological role of serotonin receptors in motor nuclei. (5) Studies on adrenergic and opiate receptors in the locus coeruleus. In general, the results show that psychotogenic drugs have powerful direct or indirect actions upon monoaminergic neurons; such actions may mediate the behavioral effects of these drugs.